Duke researchers have found a way to speed up the production of flu vaccines and make them more effective against seasonal flu virus strains.
Many vaccine companies grow the influenza virus inside of a chicken egg, where a protein called hemagglutinin, or HA, often mutates and causes the vaccine to lose some of its effectiveness. Researchers developed a new way to prompt the virus to express two copies of the HA protein, one specialized to function in the egg and the other in humans. This would prevent the human HA from adapting to the chicken egg and enhance the effectiveness of the vaccine.
“We found that this process is very effective. We can grow the virus with two copies of the HA gene in the chicken egg without it acquiring mutations,” said Nicholas Heaton, assistant professor of molecular genetics and microbiology in the School of Medicine.
Heaton explained the two primary reasons behind the flu vaccine's "traditionally low efficacy." First, the World Health Organization must predict which flu strains will be prevalent in humans during flu season. This means that an incorrect selection of strain could lead the vaccine to be ineffective even if properly manufactured.
Second, the practice of taking a human flu virus and growing it in a chicken egg can also generate problems, Heaton said. The virus may undergo mutations within the egg and come out with a mutated HA protein, limiting the vaccine's ability to activate the human immune system.
“The idea that taking the human virus and inserting it into a chicken egg—an obviously different environment—for growth is what our research studies,” Heaton noted. “When the vaccine is administered, people create a strong immune response to what they’ve been exposed to, which is a weird egg-adapted version of the human virus."
Heaton and his team's solution to the second part of the problem was to develop the technology that allowed the small genome of the human influenza virus to accommodate and express more than one HA gene.
“It’s very hard to manipulate human influenza viruses. To insert another hemagglutinin protein grows the genome’s size by about 20 percent," Heaton said. "The methodology of doing so wasn’t well known in the field."
There is a lot to be done moving forward before the technology can be implemented into seasonal influenza vaccines.
“The goal is to now show that on a year-to-year basis, our methodology is doing something. Nobody has had a mechanism to do a side-to-side comparison,” Heaton noted. “We know that the flu shot produces antibodies within a person that recognize only the chicken egg-grown virus. No one has formally shown how much better the protection would be if all your antibodies were given the correct human virus because there was no way to do so before this technology”.
The next step is to generate the mixture of four viruses that are currently in the flu shot. After generating the viruses, Heaton said the new technology needs to be implemented.
“We will have to quantify how much better the virus grows using our technology, how much better the immune response is and how much more protective it proves to be,” he said.